Human Molecular Genetics, 2000, Vol. 9, No. 15 2263-2273
© 2000 Oxford University Press
Two imprinted gene mutations: three phenotypes
Medical Research Council, Mammalian Genetics Unit, Harwell, Didcot, Oxfordshire OX11 0RD, UK
Genetic modifications of imprinted genes have been generated in the mouse to investigate the regulation of their expression. They show classical imprinted gene inheritances. Here we describe two imprinted gene mutations deriving from mutagenesis experiments. One is expressed only when transmitted through males. It causes a prenatal growth retardation which resembles that of the Igf2 knockout and maps close to the locus on chromosome 7. Differences from the knockout, which include an abnormal head phenotype, homozygous lethality, and an inability to rescue a Tme (Igf2r-deficient) lethality, suggest that Igf2 itself may not be directly affected. The second mutation maps close to the Gnas cluster of imprinted genes on distal chromosome 2. It gives two distinct phenotypes according to parental origin, a gross neonatal oedema with microcardia and a postnatal growth retardation. The oedema phenotype is effectively lethal and resembles that of mice with paternal partial disomy for distal chromosome 2, as well as that of mice having a maternally derived Gnas exon 2 knockout. However, the second growth retardation phenotype differs from that of the maternal partial disomy and the paternal knockout. A hypothesis to explain the phenotypes associated with the three genotypes based on the Nesp/Nespas sense/antisense and Gnasxl transcripts in the Gnas cluster is offered.
+ To whom correspondence should be addressed. Tel: +44 1235 834393: Fax: +44 1235 834776; Email: b.cattanach@har.mrc.ac.uk
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Wadhawan, B. Dickins, and A. Nekrutenko Wheels within Wheels: Clues to the Evolution of the Gnas and Gnal Loci Mol. Biol. Evol., December 1, 2008; 25(12): 2745 - 2757. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Krechowec and A. Plagge Physiological Dysfunctions Associated with Mutations of the Imprinted Gnas Locus Physiology, August 1, 2008; 23(4): 221 - 229. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M D Fray, A R Pickard, M Harrison, and M T Cheeseman Upgrading mouse health and welfare: direct benefits of a large-scale rederivation programme Lab Anim, April 1, 2008; 42(2): 127 - 139. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Plagge, G. Kelsey, and E. L Germain-Lee Physiological functions of the imprinted Gnas locus and its protein variants G{alpha}s and XL{alpha}s in human and mouse J. Endocrinol., February 1, 2008; 196(2): 193 - 214. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Xie, A. Plagge, O. Gavrilova, S. Pack, W. Jou, E. W. Lai, M. Frontera, G. Kelsey, and L. S. Weinstein The Alternative Stimulatory G Protein {alpha}-Subunit XL{alpha}s Is a Critical Regulator of Energy and Glucose Metabolism and Sympathetic Nerve Activity in Adult Mice J. Biol. Chem., July 14, 2006; 281(28): 18989 - 18999. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Chen, O. Gavrilova, J. Liu, T. Xie, C. Deng, A. T. Nguyen, L. M. Nackers, J. Lorenzo, L. Shen, and L. S. Weinstein Alternative Gnas gene products have opposite effects on glucose and lipid metabolism PNAS, May 17, 2005; 102(20): 7386 - 7391. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Plagge, A. R. Isles, E. Gordon, T. Humby, W. Dean, S. Gritsch, R. Fischer-Colbrie, L. S. Wilkinson, and G. Kelsey Imprinted Nesp55 Influences Behavioral Reactivity to Novel Environments Mol. Cell. Biol., April 15, 2005; 25(8): 3019 - 3026. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. M. Cattanach, C. V. Beechey, and J. Peters Interactions Between Imprinting Effects in the Mouse Genetics, September 1, 2004; 168(1): 397 - 413. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Abramowitz, D. Grenet, M. Birnbaumer, H. N. Torres, and L. Birnbaumer XL{alpha}s, the extra-long form of the {alpha}-subunit of the Gs G protein, is significantly longer than suspected, and so is its companion Alex PNAS, June 1, 2004; 101(22): 8366 - 8371. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Holmes, C. Williamson, J. Peters, P. Denny, RIKEN GER Group, GSL Members, and C. Wells A Comprehensive Transcript Map of the Mouse Gnas Imprinted Complex Genome Res., June 1, 2003; 13(6): 1410 - 1415. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Hikichi, T. Kohda, T. Kaneko-Ishino, and F. Ishino Imprinting regulation of the murine Meg1/Grb10 and human GRB10 genes; roles of brain-specific promoters and mouse-specific CTCF-binding sites Nucleic Acids Res., March 1, 2003; 31(5): 1398 - 1406. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Davies, L. Bowden, P. Smith, W. Dean, D. Hill, H. Furuumi, H. Sasaki, B. Cattanach, and W. Reik Disruption of mesodermal enhancers for Igf2 in the minute mutant Development, January 4, 2002; 129(7): 1657 - 1668. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. S. Weinstein, S. Yu, D. R. Warner, and J. Liu Endocrine Manifestations of Stimulatory G Protein {alpha}-Subunit Mutations and the Role of Genomic Imprinting Endocr. Rev., October 1, 2001; 22(5): 675 - 705. [Abstract] [Full Text] [PDF]
|
|